Immunological adjuvants are substances that, when administered together with an antigen, have the capacity to augment the immune response to the antigen. When used as a component in a vaccine formulation, the adjuvant improves the immunogenicity of the vaccine in the sense that it will enhance the immune response of the vaccinated subject, thereby reducing the amount of the vaccine component, or reducing the number of administrations needed to induce the desired immune response.
The induced effector immune response may either be of a humoral nature, i.e. an antibody response, or of a cellular nature, i.e. a cytotoxic T-cell response, or the effector response may be a mixture of both. Both cellular and humoral immune responses require help from T helper lymphocytes. Adjuvants that cause inflammation or induce pro-inflammatory cytokines will induce a Type-1 T helper response (Th1) involving production of IL-12, IL-2 and INFγ. These cytokines support induction of cytotoxic T-lymphocyte (CTL) responses, neutrophil inflammation and Th1 antibody responses, such as IgG1 and IgG3. Non-inflammatory adjuvants are more likely to induce a Type-2 helper response (Th2) involving production of the cytokines IL-4, IL-5 and IL-10. These cytokines can down-regulate Th1 responses, and promote induction of Th2 antibodies such as IgE and IgG4 as well as some cellular responses such as eosiniphilia.
Although adjuvants have been applied in the field of immunology and vaccine technology for many years, the underlying mechanisms of action are not completely understood. This has certainly complicated targeted research for identifying new adjuvant candidates.
Several substances have been or are currently being investigated for their adjuvant properties. A few examples are aluminium salts, PLG (polylactide co-glycolide), oil in water emulsions such as MF59 (a squalene in water emulsion), Quil A, Qs-21 and ISCOMs. However, many of the tested adjuvants have several drawbacks, including ineffectiveness with some antigens, contact hypersensitivity, subcutaneous nodules, and granulomatous inflammation. Others still await critical evaluation in clinical trials.
Thus, there is still a strong need for improved or safer adjuvants which can be used in human vaccines.